Radiofrequency, Cryoablation, and Pulsed Field Ablation for Atrial Fibrillation: Mechanisms, Preclinical Evidence,...

Catheter ablation has become a cornerstone therapy for atrial fibrillation, with pulmonary vein isolation as its mechanistic foundation. Radiofrequency ablation and cryoablation, the two established thermal technologies, have demonstrated robust efficacy across multiple randomized trials but remain limited by collateral tissue injury inherent to heat- or cold-mediated lesion formation. Pulsed field ablation has recently emerged as a novel non-thermal energy source based on irreversible electroporation, offering myocardial-selective injury with relative sparing of adjacent structures. This review synthesizes evidence across three complementary domains: fundamental studies; preclinical evidence; and clinical data supporting radiofrequency ablation, cryoablation, and pulsed field ablation for atrial fibrillation. We summarize mechanistic differences in lesion formation, key animal studies that established safety and efficacy profiles, and pivotal randomized clinical trials, including recent head-to-head comparisons and meta-analyses of randomized controlled trials. By synthesizing these levels of evidence, the review aims to place recent clinical results into a mechanistic and translational context. Available evidence demonstrates that pulsed field ablation achieves rhythm-control efficacy comparable to radiofrequency and cryoablation while offering procedural efficiency and a potentially improved safety profile. However, long-term durability data and broader experience remain limited. Understanding the strengths and limitations of each ablation modality is essential for informed clinical decision-making as non-thermal ablation technologies enter routine practice.